Bidirectional modulatory effect of orphanin FQ on morphine-induced analgesia: Antagonism in brain and potentiation in spinal cord of the rat

1. The present study was designed to investigate further the effects of the newly discovered orphanin FQ (OFQ) - the endogenous ligand for the orphan opioid receptor (called, e.g., ORL₁ and LC132) - on pain modulation in the rat. We used the tail-flick assay as a nociceptive index. 2. When injected into a cerebral ventricle, OFQ (4 fmol-10 nmol) has no effect on basal tail-flick latency by itself at any dose, but dose-dependently antagonizes systemic morphine analgesia (400 fmol-50 nmol). 3. Injected intrathecally, OFQ (3 and 10 nmol) displayed an analgesic effect without producing motor dysfunction, and potentiated morphine analgesia (1 and 10 nmol). 4. The anti-opioid effect of OFQ in rat brain and the high level of expression of LC132/ORL₁ receptor in the locus coeruleus indicated a possible role of OFQ in the precipitation of opiate withdrawal symptoms. However, no such precipitation was observed by OFQ in morphine-dependent rats.